Selected 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitors. A look into their use and potential in pre-diabetes and type 2 diabetes.

Objectives. This review assesses the comparative safety and efficacy of selected 3-hydroxy-3-methylglutaric acid coenzyme A inhibitors (statins, cinnamic acids. 3-hydroxy-3-methyl glutaric acid) on the pre-onset type 2 diabetes (PT2D) and post-onset type 2 diabetes (T2D)-related cluster of seven features (central obesity, hyperglycemia, hypertension, dyslipidemia, pro-thrombosis, oxidation and inflammation). Methods. Google scholar and PubMed were searched for statin*, flaxseed lignan complex (FLC), cinnamic acid (CA)*, and 3-hydroxy-3-methylglutaric acid (HMGA) in conjunction with each of PT2D, T2D and the cluster of seven. An introduction was followed by findings or absence thereof on the impacts of each of statins, FLC, CAs and HMGA on each member of the cluster of seven. Results. Pravastatin manages three features in PT2D, while a number of the statins improve five in T2D. FLC is negative in PT2D but controls four in T2D; it is not clear if the CAs and HMGA in FLC play a role in this success. CAs have potential in six and HMGA has potential in three of the cluster of seven though yet CAs and HMGA are untested in PT2D and T2D in humans. There are safety concerns with some statins and HMGA but FLC and CAs appear safe in the doses and durations tested. Conclusions. Selected statins, FLC, CAs and HMGA can manage or have a potential to manage at least three features of the cluster of seven. Most of the literature-stated concerns are with select statins but there are concerns (one actual and two potential) with HMGA.

The polypharmacy reduction potential of cinnamic acids and some related compounds in pre- and post-onset management of type 2 diabetes mellitus.

OBJECTIVES: This review assesses the polypharmacy reduction potential of cinnamic acids (CAs) and some related compounds in managing three or more of the cluster of seven, pre- and post-type 2 diabetes mellitus (T2DM)-related features (central obesity, hyperglycemia, hypertension, dyslipidemia, pro-thrombosis, oxidation, and inflammation). METHODS: Google scholar and Pubmed were searched for cinnam*, chlorogenic acid, ferulic acid, and caffeic acid in conjunction with each of pre- and post-onset T2DM, central obesity, hyperglycemia, hypertension, dyslipidemia, pro-thrombosis, oxidation, and inflammation. The study was divided into an introduction followed by findings on the impacts of each of the CAs including trans-CA acid, the E isomer of a CA-based thiazolidinedione and a metabolite of that isomer, as well as p-methoxy CA, various cinnamic amides and some other CA-related compounds (chlorogenic acid, cinnamaldehyde, ferulic and caffeic acid). RESULTS: Trans-CA has a potential to manage three, while each of chlorogenic acid, cinnamalde-hyde, caffeic acid and ferulic acid has a potential to manage all seven members of the cluster. Other CA-related compounds identified may manage only one or two of the cluster of seven. CONCLUSIONS: Much of the work has been done in animal models of pre- and post-onset T2DM and non-pre- or post-onset T2DM humans and animals, along with some cell culture and in vitro work. Very little work has been done with human pre- and post-onset T2DM. While there is potential for managing 3 or more members of the cluster with many of these compounds, a definitive answer awaits large pre- and post-T2DM onset clinical trials with humans.

Lignans' Potential in Pre and Post-onset Type 2 Diabetes Management.

INTRODUCTION: Type 2 Diabetes (T2D) cases continue to rise dramatically despite efforts to get people to exercise and eat with a view to health and combatting the cluster of 7 issues (central obesity (elevated waist circumference), hyperglycaemia, hypertension, dyslipidemia, pro-thrombotic state, increased oxidation (including Low-density Lipoprotein (LDL)) and the pro-inflammatory state associated with pre- and post-onset T2D. BACKGROUND: There are numerous medications available to deal with these seven major issues. However, each medication currently available manages a maximum of two cluster members at a time. Consequently, polypharmacy is frequently required to manage the cluster of seven. Polypharmacy brings with it high financial costs for numerous medications, the risk of poor compliance (particularly so in older patients), side effects and drug interactions. Thus, there is a search for new agents that reduce the high costs and risks of polypharmacy while at the same time combatting three or more of the cluster of seven. There is very limited evidence to suggest that one or more lignans may efficaciously and safely, in the short and long term, manage at least three of the cluster of seven, pre- and post-T2D onset, thus reducing polypharmacy. However, multi-centre, large clinical trials are required before any definitive conclusions about these lignans can be reached regarding their safe and efficacious polypharmacy reduction potential, both long and short-term, in pre and post-onset T2D management. CONCLUSION: It is concluded that some lignans appear to have the potential to manage at least three members of the cluster of seven in pre- or post-T2D onset and hence reduce polypharmacy but much more investigation is required to confirm if such is the case. At the moment, there is not enough evidence that any of the lignans will, in the long or short term, safely and efficaciously manage the cluster of seven via polypharmacy reduction.

National Survey of Indigenous primary healthcare capacity and delivery models in Canada: the TransFORmation of IndiGEnous PrimAry HEAlthcare delivery (FORGE AHEAD) community profile survey.

BACKGROUND: There is a significant deficiency of national health information for Indigenous peoples in Canada. This manuscript describes the Community Profile Survey (CPS), a community-based, national-level survey designed to identify and describe existing healthcare delivery, funding models, and diabetes specific infrastructure and programs in Indigenous communities. METHODS: The CPS was developed collaboratively through FORGE AHEAD and the First Nations and Inuit Health Branch of Health Canada. Regional and federal engagement and partnerships were built with Indigenous organizations to establish regionally-tailored distribution of the 8-page CPS to 440 First Nations communities. Results were collected (one survey per community) and reported in strata by region, with descriptive analyses performed on all variables. Results were shared with participating communities and regional/federal partners through tailored reports. RESULTS: A total of 84 communities completed the survey (19% response rate). The majority of communities had a health centre/office to provide service to their patients with diabetes, with limited on-reserve hospitals for ambulatory or case-sensitive conditions. Few healthcare specialists were located on-site, with patients frequently travelling off-site (> 40 km) for diabetes-related complications. The majority of healthcare professionals on-site were Health Directors, Community Health Nurses, and Home Care Nurses. Many communities had a diabetes registry but few reported a diabetes surveillance system. Regional variation in healthcare services, diabetes programs, and funding models were noted, with most communities engaging in some type of innovative strategy to improve care for patients with diabetes. CONCLUSIONS: The CPS is the first community-based, national-level survey of its kind in Canada. Although the response rate was low, the CPS was distributed and successfully administered across a broad range of First Nations communities, and future considerations would benefit from a governance structure and leadership that strengthens community engagement, and a longitudinal research approach to increase the representativeness of the data. This type of information is important for communities and regions to inform decision making (maintain successes, and identify areas for improvement), strengthen health service delivery and infrastructure, increase accessibility to healthcare personnel, and allocate funding and/or resources to build capacity and foster a proactive chronic disease prevention and management approach for Indigenous communities across Canada. TRIAL REGISTRATION: Current ClinicalTrial.gov protocol ID NCT02234973 . Registered: September 9, 2014.

Best Practices for the Prevention and Management of Diabetes and Obesity-Related Chronic Disease among Indigenous Peoples in Canada: A Review.

OBJECTIVES: To carry out a systematic review of interventions that have aimed at improving screening, treatment, prevention and management of type 2 diabetes and obesity-related chronic disease in Indigenous communities in Canada from 2008 to 2014, with the aim of identifying current best practices. METHODS: A comprehensive literature review was carried out through an electronic database search using Medline, EMBASE, PubMED and Google scholar. RESULTS: We identified 17 publications, comprising 13 evaluated interventions. Of them, 7 were school-based programs focused on children, 5 focused on adults, and 1 included both adults and children. Most interventions aimed at encouraging behaviour change, especially dietary change, but did little to address the underlying context of systemic marginalization and colonialism experienced in many Indigenous communities. Interventions focused on improving fitness were more effective than those aimed at dietary change. Overall, we found a range of successes among these interventions. Those that met with limited success reported that complex social issues and poverty presented challenges to effective intervention work in these communities. Participatory action research methods and community ownership of the intervention were found to be essential for project success. CONCLUSIONS: Diabetes-focused intervention research in Indigenous communities appears to be a low priority for Canadian funders and policymakers. More intervention research is urgently needed in these communities. To be effective, this work must take an approach that is historically deep and sufficiently broad as to enable the ideologic, policy and institutional changes necessary in order to achieve true equity. This will involve addressing colonialism, racism and social exclusion as broader determinants of health.

The role of consumption of alpha-linolenic, eicosapentaenoic and docosahexaenoic acids in human metabolic syndrome and type 2 diabetes--a mini-review.

The human metabolic syndrome and its frequent sequela, type 2 diabetes are epidemic around the world. Alpha-linolenic acid (ALA, 18:3 n-3), eicosapentaenoic acid (EPA, 20:5 n-3) and docosahexaenoic acid (DHA, 22:6 n-3) consumption ameliorates some of these epidemics' features thus leading one to question if consumption of EPA and DHA, and their metabolic precursor ALA reduce the conversion of metabolic syndrome to type 2 diabetes and reduce the major cause of death in the metabolic syndrome and type 2 diabetes-myocardial infarction. Contributing to myocardial infarction are metabolic syndrome's features of dyslipidemia (including elevated total cholesterol and LDL-c), oxidation, inflammation, hypertension, glucose intolerance, overweight and obesity. Inflammation, glucose and lipid levels are variously influenced by disturbances in various adipocytokines which are in turn positively impacted by n-3 polyunsaturated fatty acid consumption. Type 2 diabetes has all these features though elevated total cholesterol and LDL-c are rarer. It is concluded that EPA and DHA consumption significantly benefits metabolic syndrome and type 2 diabetes primarily in terms of dyslipidemia (particularly hypertriglyceridemia) and platelet aggregation with their impact on blood pressure, glucose control, inflammation and oxidation being less established. There is some evidence that EPA and/or DHA consumption, but no published evidence that ALA reduces conversion of metabolic syndrome to type 2 diabetes and reduces death rates due to metabolic syndrome and type 2 diabetes. ALA's only published significance appears to be platelet aggregation reduction in type 2 diabetes.